The research proposed will be concerned with how nociceptive information is signalled to the brain and how nociceptive transmission can be interrupted. The specific projects to be done involve 1) the organization of ascending somatosensory pathways transmitting nociceptive information; 2) the organization of pathways descending from the brain that influence the activity of ascending nociceptive pathways; and 3) the processing of nociceptive information by neurons of the ventral posterior lateral (VPL) nucleus of the thalamus. Major emphasis will be placed on the structure, synaptic connections, biophysical properties, and receptive fields of spinothalamic tract (STT) cells. However, experiments will also be done to examine the activity of neurons in other putative nociceptive tracts, such as the spinoreticular, spinocervical and postsynaptic dorsal column pathways. Descending control pathways to be examined will include systems originating in the cerebral cortex, red nucleus, nucleus raphe magnus, periaqueductal gay and reticular formation. The effect of opiate substances on STT cells will be studied. Responses of neurons in the VPL nucleus to volleys in A delta and C fibers will be recorded, and the effects of tracts ascending in different parts of the spinal cord white matter will be distinguished. The animals to be used include monkeys (Macaca fascicularis), since the nociceptive pathways in subhuman primates are more likely to resemble those in the human than are nociceptive pathways in other commonly used laboratory animals. However, an effort will be made to examine the response properties of STT cells in the cervical spinal cord in the cat to see if these cells are comparable to STT cells in the monkey. It is hoped that the results of these studies will be useful for a better understanding of pain mechanisms and of pain therapy in humans.